In our studies of the psychoactive properties of thyrotropin releasing hormone (TRH) in rabbits, we made several important observations which require further investigation. These include: (1) the extremely potent analeptic property of TRH against various CNS depressants; (2) the ability of centrally administered TRH to produce marked increases in gastrointestinal motility; and (3) the ability of centrally administered TRH to produce a vasopressor response which appears not to be mediated via the sympathetic nervous system. All of these effects of TRH are produced with microgram doses administered into the lateral ventricles, but also are not seen with even milligram doses intravenously. We have found that the first two responses of TRH described above mediated via cholinergic mechanisms, and therefore propose to localize the brain sites at which these originate. We also intend to study acetylcholine turnover in different brain regions to establish a neurochemical correlate with the behavioral and physiological responses to TRH. The studies on the cardiovascular actions of centrally administered TRH will be continued by determining where in the peripheral vascular system the response is taking place. This will be accomplished by determining blood flow thoough different parts of the body. The radioactive microsphere technique for the determination of blood flow and cardiac output will be employed to attain this information. We fuuther intend to localize the brain site at which TRH is initiating this cardiovascular response by microinjecting small quantities of the peptide into various brain regions.